Pregnant couples’ attitude toward extended pre-conceptional genomic screening

Aim To determine the attitudes of pregnant couples toward carrier screening genomic tests. Methods A validated 22-item questionnaire was offered in person by medical staff to pregnant women ≥32 weeks’ gestation and their partners attending prenatal classes from May to July 2014. The questionnaire inquired about demographic data, interest in various forms of genetic carrier screening tests, and genetic literacy. Results Of 497 respondents, 69% expressed strong interest in carrier screening. The interested respondents exhibited substantial support for screening for common (82%) or all known genetic diseases (79%), as well as for treatable (79%) and untreatable diseases (85%). The majority of respondents believed that genetic test results could provide them with a sense of security but also provoke anxiety and fear. They were aware that these results could affect their perspective on life, work, and the atmosphere within their family, and acknowledged the potential effect on their relationship with their partner. However, none of these concerns diminished their desire to learn about their carrier status. Respondents with higher genetic literacy exhibited greater interest in screening tests (P = 0.006). More non-religious respondents compared with practicing religious respondents (P = 0.002), and more respondents with higher education compared with those with lower education, expressed interest in screening (P = 0.003). Conclusion Most respondents expressed considerable interest in receiving information about their carrier status through genetic tests.


Aim
To determine the attitudes of pregnant couples toward carrier screening genomic tests.
Methods A validated 22-item questionnaire was offered in person by medical staff to pregnant women ≥32 weeks' gestation and their partners attending prenatal classes from May to July 2014.The questionnaire inquired about demographic data, interest in various forms of genetic carrier screening tests, and genetic literacy.

Results
Of 497 respondents, 69% expressed strong interest in carrier screening.The interested respondents exhibited substantial support for screening for common (82%) or all known genetic diseases (79%), as well as for treatable (79%) and untreatable diseases (85%).The majority of respondents believed that genetic test results could provide them with a sense of security but also provoke anxiety and fear.They were aware that these results could affect their perspective on life, work, and the atmosphere within their family, and acknowledged the potential effect on their relationship with their partner.However, none of these concerns diminished their desire to learn about their carrier status.Respondents with higher genetic literacy exhibited greater interest in screening tests (P = 0.006).More non-religious respondents compared with practicing religious respondents (P = 0.002), and more respondents with higher education compared with those with lower education, expressed interest in screening (P = 0.003).

Conclusion
Most respondents expressed considerable interest in receiving information about their carrier status through genetic tests.
Carrier screening is a genetic testing method used to identify individuals, typically asymptomatic ones, who carry a gene mutation for an autosomal recessive or X-linked recessive disorder.Historically, carrier screening focused on the most prevalent recessive disorders, such as cystic fibrosis, Tay-Sachs syndrome, and thalassemia (1)(2)(3).Advancements in genotyping technology and reduced costs have expanded the range of disorders that can be screened for.Today, many commercial laboratories worldwide offer carrier screening panels that include over 100 less common or even extremely rare disorders (4,5).The expanded carrier screening approach has sparked discussions on technical, ethical, legal, and social considerations (6,7).Carrier screening, whether offered by commercial entities or national health care systems, should only be provided to target populations following responsible implementation procedures (8)(9)(10).This includes conducting thorough research on public attitudes and preferences.
The primary goal of carrier screening is to facilitate informed reproductive decision-making (8).Consumers should receive comprehensive information on the pros and cons of extended carrier screening.Pre-conceptional carrier screening, akin to genetic testing in general, has garnered substantial public support (8,(11)(12)(13).Nevertheless, there have been instances where individuals do not express a desire for carrier screening (14).Previous studies have predominantly focused on more common and severe disorders within populations where recessive diseases are prevalent.The focus of the present study is to determine the pregnant couples' attitude toward extended carrier screening, with a specific emphasis on discerning the factors associated with participation in pre-conceptional carrier couple screening.

Study design and respondents
We developed a questionnaire and distributed it anonymously among pregnant women of Slovene nationality and their partners attending prenatal classes at the Gynecological Clinic in Ljubljana from May to July 2014.Prenatal classes offer education for women in the later stages of pregnancy, covering topics such as childbirth, newborn care, and relevant information.Pregnant women receive oral invitations to attend these classes during their regular check-ups with their gynecologist.The questionnaires were distributed personally to the attendees during one of the sessions, and partners did not need to be The questionnaire consisted of three parts.The first part inquired about demographic data (Table 1).The second part consisted of 15 statements designed to assess participants' general knowledge about genetic disorders.The first statement addressed the general prevalence of genetic/ heritable diseases, with participants receiving zero points for selecting "very rare (less than 1/1,000,000), " one point for "rare (less than 1/10,000), " and two points for "frequent (more than 1/1000)".Subsequently, a series of statements assessed participants' perceptions of the heritability of 14 disease groups (eg, cancer, epilepsy, infections, deafness, infertility, hemophilia, neuro-muscular diseases, etc).The responses ranged from "1 -the disease is not at all heritable" to "5 -the disease is highly heritable." Participants were awarded a point if their answer deviated by no more than one point from the norm, which was established as the mode of answers provided by five medical doctors working as genetic counselors.The total score for genetic literacy ranged from 0 to 16 points.
The third part constituted the main section of the questionnaire and consisted of one closed question and 21 Likert-type statements.Respondents were asked to rate their level of agreement from 1 ("I totally disagree/I am not at all interested") to 5 ("I totally agree/I am very interested").
In conjunction with question 22, the respondents were presented with the following informative paragraph: "Preconception genetic screening is performed on healthy parents-to-be.With it, we can determine the probability www.cmj.hr that their children will suffer from a particular genetic disease.At the same time, it can provide new information on the probability that the parents themselves will develop a genetic disease in the future.When investigating the genome of every individual, we can expect to find 2-3 genetic variations that can predispose them to serious genetic illness and 50-100 genetic variations of which the precise importance is unknown.In case the parents-to-be decide on preconception genetic screening (meant for the wellbeing of the planned child), the results can give them new information about the risk that they will become affected by a genetic disease." The statements were categorized into eight sections (Table 2).

Statistical analysis
Descriptive statistics were employed to present the questionnaire results.The normality of data distribution was assessed visually by means of a quantile-quantile plot.The relationship between demographic factors and respondents' attitudes was evaluated with a χ 2 test or a Fisher ex-act test.To assess the differences in genetic knowledge score and responses to Likert items across demographic groups, independent-samples t tests and analysis of variance were conducted.Multiple pairwise comparisons were performed with the Hochberg test.A P value of <0.05 was considered statistically significant.The analysis was performed with SPSS 25.0 (IBM Corp., Armonk, NY, USA).

Demographics
A total of 497 respondents took part in the survey (197 couples, comprising a male and a female partner).The respondents' demographics are outlined in Table 1.

Genetic literacy
Individuals with higher education (college or more) achieved a higher average genetic literacy score compared with those with lower education (11.2 vs 10.3; P = 0.004).Furthermore, respondents with a higher mean genetic literacy score displayed more interest in general genetic screening (Q1, P = 0.006), screening for common genetic diseases (Q2, P = 0.016), and screening for variants that may cause developmental abnormalities of the fetus or diseases in the offspring (Q4, P = 0.008) (Table 1).
Respondents with a higher score were less supportive of pregnancy termination in the case of pathological prenatal screening results (Q10, P = 0.023).They also felt less secure about the test results (Q14, P = 0.018) and were less likely to believe that genetic screening should be covered by national health insurance policies (Q21, P = 0.013).

Interest in genetic screening
The responses to all the questions in the questionnaire are shown in Table 2.
Section 1 -General interest in genetic screening to prevent heritable diseases in offspring.Among the 497 respondents, 339 (69%) expressed general interest in genetic screening, 153 (31%) showed no interest or had a neutral stance, while five respondents did not answer this question.The responses to this question were significantly influenced by religiousness (P = 0.002), level of education (P = 0.003), and age (P = 0.046).Specifically, more non-religious respondents than practicing religious respondents showed interest in genetic screening (77.6% vs 59.8%).Also, interest in genetic screening was shown by more respondents with college or higher education than those with lower education (74.2% vs 60.3%).Respondents in the age group of 36 and above showed higher interest in genetic screening than those in the age group of 18-25 (mean 4.1 vs 3.5).
The general interest in genetic screening was positively associated with perceived benefits, feelings of safety provided by the test results, and willingness to participate financially (P < 0.001 for each).Additionally, the respondents who believed that the genetic test should be covered by national health insurance policy also demonstrated greater interest in genetic screening (P = 0.032).
Conversely, the extent of anxiety regarding the test results was inversely related to the general interest in genetic screening (P = 0.008).
Only those respondents who agreed or totally agreed to the question in Section 1 were asked to respond to the items in Sections 2 and 3.  Positive attitude (answer 4 or 5), % www.cmj.hrSection 6 -Psychosocial implications.Overall, 31%-53% respondents believed that genetic test results could have psychological effects on their private or social life.Fewer patients from the first pregnancy group agreed or strongly agreed that genetic results could affect the relationship with their partner compared with those who already had one or more pregnancies (27.7% vs 42.1%; P = 0.007).Fewer respondents in the first pregnancy group agreed or strongly agreed that genetic results could affect employability and insurance issues compared with those who already had one or more pregnancies (45.5% vs 58.5%; P = 0.007).
Section 7 -Financial aspect.The majority of respondents (76.6%) believed that genetic tests should be covered by national health insurance policies.Respondents who already had one or more children were more supportive of the statement that the cost should be fully covered by national insurance company compared with respondents in their first pregnancy (86.2% vs 74.1%, respectively; P < 0.001).A total of 44% respondents were willing to financially participate in pre-conceptional carrier screening tests, and 65.7% were ready to pay between 1 and 100 €.
The respondents who were more supportive of the statements that genetic screening tests were important, comforting, useful, provided an improved sense of security, affected the attitude toward life, work, and family, and should be paid by users were more likely to pay 1000 € or more compared with those who disagreed or had a neutral opinion about these statements (37.4% vs 25.7%, P = 0.025; 40.5% vs 26.8%, P = 0.004; 39.7% vs 20%, P < 0.001; 38.2% vs 25.4%, P = 0.011; 43.1% vs 23.6%, P < 0.001; and 46% vs 23.8%, P < 0.001, respectively).Section 8 -Relevance for parent's health.Overall, 52.9% of participants agreed or strongly agreed that the knowledge that genetic screening results could also provide information about their own risk of developing a genetic disease would affect their decision to undergo genetic testing.One-third of the respondents were undecided on this matter.None of the demographic factors significantly influenced the responses to this statement.

Overall results
The study found most of the participants to be interested in genetic carrier screening.Two demographic factors directly affected this interest level.Religiosity diminished the interest in genetic carrier screening, while higher educational level increased it.
As anticipated, religious status strongly affected responses regarding termination of pregnancy if a pathogenic variant was to be prenatally identified in the fetus.However, as we asked about a hypothetical situation without providing data on the severity of the predicted disease, it is not surprising that around a third of the respondents across all religious groups were undecided.Nevertheless, 30% of practicing religious respondents denied the possibility of abortion, compared with only a minority of non-religious and non-practicing religious respondents.These statements were answered only by respondents interested in genetic screening.Since the level of interest in genetic screening was affected by religious beliefs, full participation might have yielded different results.However, we generally focused on the preferences of those with the highest interest in genetic screening tests.
As expected, interest in genetic screening was positively related to the overall opinion about genetic tests (items from section 4 -perceived benefits) and the belief in the sense of security that the test results can provide.Respondents who showed greater interest in genetic screening were also more willing to pay for the service and believed that national health insurance should fund it.Conversely, those who experienced higher levels of anxiety regarding test results and feared potential pathologic findings were less interested in genetic screening.
The majority of respondents believed that genetic test results could impact their perspectives on life, work, and family, as well as the relationship with their partner.The responses in this section showed less positive attitudes than responses in the other sections, likely due to the significant implications associated with the items.Importantly, the results in this section were not related to any of the items assessing the interest in genetic screening.This suggests that while respondents were aware of the potential psychosocial implications of genetic tests, these considerations did not have a major role in their decision to undergo genetic carrier screening tests.These results suggest that interest in genetic screening is driven mainly by the reassurance provided by a negative test result.On the other hand, it is discouraged by the fear of a confirmed pathological finding and the difficulty of making decisions regarding the termination of pregnancy.
Although there are still significant challenges and barriers to the successful implementation of expanded carrier screening programs, including the lack of understanding of genetic conditions among the general public (15), other studies have reported relatively high interest in genetic screening but also reluctance due to fear (8,16,17).Furthermore, in a study that assessed couples' experience with expanded carrier screening, all participants stated that they would opt for the test again, and 80% would recommend it to others (18).

Effect of genetic knowledge
Respondents' general genetic knowledge was relatively high, which is similar to some studies (12,16), although other authors reported low genetic literacy among both patients and medical practitioners (8).
As expected, participants with higher education levels scored higher on genetic literacy.A higher genetic literacy score was inversely related to the support for pregnancy termination and the feelings of safety.Additionally, higher scores indicated a greater overall interest in genetic screening.Education influenced the general interest in genetic screening in two ways: first, through its impact on the genetic score, and second, by directly reducing fear surrounding the test results.While the former had a diminishing effect, higher education was generally associated with greater interest in genetic screening.A positive relationship between knowledge and interest in genetic screening was also reported by other studies (16,19).
Half of our respondents stated that the informative paragraph provided alongside question 22 significantly affected their decision regarding genetic screening tests, while in less than 15% the interest remained unchanged.The informative paragraph provided participants with new reasons to question the predictive value of genetic tests, such as the presence of numerous genetic variations with unknown significance.It also alerted them to potential concerns, such as the possibility of receiving information about their own risk for genetic disease.This item can be interpreted as a measure of the disparity between initial expectations and the realistic utility of existing genetic screening tests.This disparity indicates an imbalance between perceived and factual knowledge, which has also been observed in other studies (20,21).Taken together, the results concerning the informative paragraph revealed that increased knowledge about the limitations of current genetic screening tests tends to decrease interest in undergoing testing.In a realistic scenario, individuals who receive appropriate pre-test counseling may experi-ence a reduction in their initial interest in genetic screening due to a better understanding of the subject matter and potential limitations.The association between knowledge and attitude is complex and was discussed also in other studies (12,22,23).A better-informed public does not necessarily equate to higher levels of support.In the words of Jallinoja et al (23): "Among those with the highest level of knowledge, there was both more enthusiasm and more skepticism than among those with the lowest level of knowledge." Our study has some limitations.The findings may not be applicable to the general population as the sample only included expectant parents who attended a prenatal education course.Attendance in this course is voluntary, so only interested parents participated.It is possible that different results regarding the genetic knowledge of parents and their attitudes toward genetic testing could be obtained compared with those in this study.However, our findings offer valuable insights into parents' attitudes toward pre-conceptional screening, especially since no similar studies have been conducted in Slovenia to date.Additionally, the current study assessed a hypothetical scenario of pre-conceptional screening.It is possible that parents might have a different view if they were faced with an actual decision.
In conclusion, the study emphasizes the significant interest in extended pre-conceptional genomic carrier screening among pregnant couples.Despite acknowledging potential challenges associated with genetic testing, the participants generally exhibited a positive attitude toward the carrier screening.

TABLE 2 .
Parental attitude toward extended pre-conceptional genomic screening When asked about the termination of pregnancy in the case of a pathological prenatal screening result, half of the respondents answered that they would most likely or definitely terminate the pregnancy.A third of the respondents remained undecided.The responses were significantly inwww.cmj.hrcreasedfeelings of safety (65%) but also anxiety and fear (67.1%).More women than men agreed that these tests increased anxiety and (71.1% vs 61%; P = 0.020), as well as more respondents with lower education compared with those with the highest education level (73.8% vs 63.7%; P = 0.040).*Described in the Respondents and Methods section.†M -arithmetic mean; Me -median.

TABLE 2 .
Continued.Parental attitude toward extended pre-conceptional genomic screening